Pain Physician 2019; 22:E55-E70 • ISSN 2150-1149

Systematic Review

Manipulation and Mobilization for

Treating Chronic Nonspecific Neck Pain: A
Systematic Review and Meta-Analysis for an
Appropriateness Panel
Ian D. Coulter, PhD1-3, Cindy Crawford, BA1, Howard Vernon, DC, PhD1,4,
Eric L. Hurwitz, DC, PhD1,5, Raheleh Khorsan, PhD3,6, Marika Suttorp Booth, MS1,
and Patricia M. Herman, ND, PhD1

From: 1RAND Corporation,
Santa Monica, CA; 2University of
California Los Angeles, School
of Dentistry, Los Angeles, CA;
3
Southern California University
of Health Sciences, Whittier, CA;
4
Canadian Memorial Chiropractic
College, Division of Research,
Toronto, ON, Canada; 5Office of
Public Health Studies, University
of Hawaii, Mānoa, Honolulu, HI;
6
Yo San University of Traditional
Chinese Medicine, Los Angeles,
CA
Address Correspondence:
Ian D. Coulter, PhD
RAND Corporation, 1776 Main
Street, Santa Monica, CA 90407
E-mail: coulter@rand.org
Disclaimer: This project is
funded by the National Center
for Complementary and
Integrative Health under Award
Number U19AT007912 and does
not necessarily represent the
official views of the National
Institutes of Health. All analyses
of data, manuscript preparation,
and presentation are the work
solely of the authors and free
of commercial input, influence,
or bias.Conflict of interest:
Each author certifies that he
or she, or a member of his or
her immediate family, has no
commercial association (i.e.,
consultancies, stock ownership,
equity interest, patent/licensing
arrangements, etc.) that might
pose a conflict of interest in
connection with the submitted
manuscript.
Manuscript received: 10-22-2018
Revised manuscript received:
01-07-2019
Accepted for publication:
01-16-2019
Free full manuscript:
www.painphysicianjournal.com
Background: Mobilization and manipulation therapies are widely used by patients with chronic
nonspecific neck pain; however, questions remain around efficacy, dosing, and safety, as well as
how these approaches compare to other therapies.
Objectives: Based on published trials, to determine the efficacy, effectiveness, and safety of
various mobilization and manipulation therapies for treatment of chronic nonspecific neck pain.
Study Design: A systematic literature review and meta-analysis.
Methods: We identified studies published between January 2000 and September 2017, by searching
multiple electronic databases, examining reference lists, and communicating with experts. We
selected randomized controlled trials comparing manipulation and/or mobilization therapies to sham,
no treatment, each other, and other active therapies, or when combined as multimodal therapeutic
approaches. We assessed risk of bias by using the Scottish Intercollegiate Guidelines Network criteria.
When possible, we pooled data using random-effects meta-analysis. Grading of Recommendations,
Assessment, Development, and Evaluation was applied to determine the confidence in effect
estimates. This project was funded by the National Center for Complementary and Integrative
Health under award number U19AT007912 and ultimately used to inform an appropriateness panel.
Results: A total of 47 randomized trials (47 unique trials in 53 publications) were included in
the systematic review. These studies were rated as having low risk of bias and included a total
of 4,460 patients with nonspecific chronic neck pain who were being treated by a practitioner
using various types of manipulation and/or mobilization interventions. A total of 37 trials were
categorized as unimodal approaches and involved thrust or nonthrust compared with sham, no
treatment, or other active comparators. Of these, only 6 trials with similar intervention styles,
comparators, and outcome measures/timepoints were pooled for meta-analysis at 1, 3, and 6
months, showing a small effect in favor of thrust plus exercise compared to an exercise regimen
alone for a reduction in pain and disability. Multimodal approaches appeared to be effective at
reducing pain and improving function from the 10 studies evaluated. Health-related quality of life
was seldom reported. Some 22/47 studies did not report or mention adverse events. Of the 25 that
did, either no or minor events occurred.
Limitations: The current evidence is heterogeneous, and sample sizes are generally small.
Conclusions: Studies published since January 2000 provide low-moderate quality evidence that
various types of manipulation and/or mobilization will reduce pain and improve function for chronic
nonspecific neck pain compared to other interventions. It appears that multimodal approaches, in
which multiple treatment approaches are integrated, might have the greatest potential impact.
The studies comparing to no treatment or sham were mostly testing the effect of a single dose,
which may or may not be helpful to inform practice. According to the published trials reviewed,
manipulation and mobilization appear safe. However, given the low rate of serious adverse events,
other types of studies with much larger sample sizes would be required to fully describe the safety
of manipulation and/or mobilization for nonspecific chronic neck pain.
Key words: Chronic neck pain, nonspecific, chiropractic, manipulation, mobilization, systematic
review, meta-analysis, appropriateness
Pain Physician 2019: 22:E55-E70

www.painphysicianjournal.com
 Pain Physician: March/April 2019: 22:E55-E70
A n estimated 66% of the population will
suffer from neck pain at some point during
their lifetime (1). In 2007, neck pain was
the second most common reason cited by patients for
using complementary and integrative medicine (CIM),
preceded only by low back pain (2). The vast majority
of neck pain is not due to organic pathology, and
thus, has been termed “nonspecific” or “mechanical.”
Nonspecific neck pain is responsible for a significant
proportion of direct health care costs, visits to health
care providers, sick leave, and the related loss of
productivity (3-5). Most nonspecific neck pain is not
associated with major disease or with neurologic signs
of nerve compression. For some patients, nonspecific
neck pain rarely, if at all, interferes with daily activities;
for others, nonspecific neck pain constitutes a major
hindrance to daily functioning (6). More than one-third
of people affected still have low grade symptoms or
recurrences more than one year after treatment, often
leading to chronic pain (7).
Many interventions are available for managing
nonspecific chronic neck pain, including analgesics as
prescribed by medical practitioners, physiotherapy,
educational modalities, exercise, and manual therapy
(4,6,8-10). Self-care management and educational
modalities are usually the initial forms of treatment
for nonspecific chronic neck pain. There is some evi-
dence that educational videos are useful for patients
with whiplash-related neck pain (11). There is little
evidence that these types of modalities are more effec-
tive compared to other conservative therapies (6,12).
Physiotherapy, exercise, and manual therapies such as
massage, chiropractic, occupational, and osteopathic
therapies, including spinal manipulation and mobiliza-
tion, are used in isolation and in conjunction with other
therapies to treat nonspecific neck pain.
There are several systematic reviews of manual
therapies, such as spinal manipulation and mobiliza-
tion, for the treatment of neck pain (5,8,13,14). Some
reviews have found that there is no evidence or insuf-
ficient evidence that spinal manipulative therapy is
superior to other standard treatments for patients with
chronic neck pain (15). However, more recent system-
atic reviews on chronic neck pain, as well as chronic low
back pain, suggest spinal manipulation and mobiliza-
tion are “viable” options for treating pain and reduc-
ing disability (8). The Bone and Joint Decade 2000-2010
Task Force (12) found that mobilization or exercise
sessions alone, or in combination with medications, are
the most beneficial treatment for short term neck pain.
E56 www.painphysicianjournal.com
Others have concluded that interventions commonly
used by manual therapy practitioners, such as chiroprac-
tic care, improve outcomes for the treatment of chronic
neck pain (16,17). The greatest increase in benefits has
been suggested for multimodal approaches, in which
multiple approaches are used together to treat chronic
neck pain (16).
The long-term benefit of manual therapy is not
well established in the literature. A systematic review
of selected CIM therapies for neck and low back pain by
Furlan et al (18), comparing CIM therapies to other ac-
tive treatments (e.g., other CIM therapy, physiotherapy,
pain medication, usual care) found that, “manipulation
and mobilization effectiveness is variable depending
on symptom duration, outcome, comparator, whether
there is exercise or general practitioner care, and follow-
up period. Although this variability can be considered
inconsistent findings, the overall evidence suggests that
manipulation and mobilization are an effective treat-
ment modality compared to other therapies” (18). The
findings of this systematic review regarding the effects
of manipulation on neck pain appear to be consistent
with both older and newer reviews (8,14).
The purpose of this systematic review was to evalu-
ate the randomized controlled trials (RCTs) published
from January 2000 through September 2017 on chronic
nonspecific neck pain, comparing the effects of ma-
nipulation and/or mobilization as therapies to those of
other active therapies (such as acupuncture, massage
therapy, exercise, etc.) to sham or no treatment, and
when combined with other therapies such as exercise
or advice commonly seen in practice. The decision to
begin with January 2000 was based on the fact that
previous systematic reviews (SRs) existed up until that
date and this represented a more rational use of our re-
sources. The goal was to not only update the evidence
base since these previous reviews reported earlier, but
to better understand the effectiveness of the various
types of manipulation and/or mobilization for treating
chronic nonspecific neck pain, and the potential impact
on patient-reported outcomes associated with pain,
disability, and health-related quality of life (HRQoL).
When there were subsets of data the authors felt were
similar enough to pool, meta-analyses were attempted.
This review was in support of a larger project investi-
gating the appropriateness of manipulation/mobiliza-
tion for the treatment of chronic low back pain and
neck pain, funded by the National Center for Comple-
mentary and Integrative Health under award number
U19AT007912. The systematic review was done to pres-
 Manipulation and Mobilization for Treating Chronic Nonspecific Neck Pain
ent to a panel of experts who were making judgments
about the appropriateness of using manipulation and/
or mobilization for the treatment of nonspecific chronic
neck pain under different clinical scenarios. This grant
was a cooperative agreement and National Institutes of
Health (NIH) also appointed an external advisory com-
mittee (EAC), who had the authority both to vote go/
no go with regard to the planned systematic review and
again to vote go/no go after reviewing the systematic
review itself. The systematic review was then presented
to an expert panel to use in their rating of the ap-
propriateness of manipulation and/or mobilization for
nonspecific chronic neck pain.
Methods
This systematic review and meta-analysis report
adhere to the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses guidelines.
Search Strategy and Data Sources
This systematic review builds on previous systematic
reviews (up through 2000) that reported the evidence
base for manipulation and mobilization for neck pain
(8,15,19,20). We searched PubMed/MEDLINE, Cochrane,
Embase, Cinahl, PsycInfo, and Index to Chiropractic
Literature (ICL) for studies published between January
2000 and September 2017. In addition, we searched ref-
erence lists and consulted with subject matter experts.
The search strategy was intentionally designed to be
broad in nature without predefining the specific popu-
lation (i.e., not using the words ‘chronic’ or ‘nonspecific’)
or intervention (i.e., spanning multiple professions). In
addition, there were no limitations placed on control/
comparators, specific outcomes, or study designs, so
that the breadth and variations across the research
could be discovered, and the literature could inform
the appropriate definitions and subgroups to consider
for analysis. Because the NIH-funded project focused on
both chronic nonspecific neck pain and chronic low back
pain, we conducted the search to meet both needs. (Fig.
1 and Table 1)
Scoping Review
A scoping review of the literature informed the defi-
nitions and categorization of studies for systematic re-
view. We categorized studies accordingly to the specific
populations, interventions, control/comparators, patient
reported outcomes, and study designs discovered in the
literature base. We excluded studies clearly not related
to neck pain or to an intervention involving mobilization
www.painphysicianjournal.com E57
and/or manipulation. We presented findings to an inter-
nal steering committee (ISC) as well as an EAC. With the
help of these committees, evidence-informed definitions
and specific eligibility criteria were devised based on the
evidence base to be used in carrying out the systematic
review and attempted meta-analysis (Table 1).
Study Selection
Six reviewers used study eligibility criteria to inde-
pendently screen the literature in duplicate (Table 1).
Disagreements about inclusion were resolved through
discussion and consensus, or ultimately by the ISC.
Eligibility criteria included: 1) a population experienc-
ing chronic (21,22) and nonspecific (23) neck pain; 2)
an intervention, with the involvement of a therapist,
consisting of either (i) manipulation (labeled as thrust),
(ii) mobilization (labeled as nonthrust), or (iii) a mul-
timodal integrative practice including manipulation
and/or mobilization components as part of the ap-
(Manipulation Osteopathic OR Chiropractic Manipulation
OR Spinal Manipulation OR Musculoskeletal Manipulation
OR Osteopathic Medicine OR Chiropractic OR manipulation
orthopedic OR mobiliz* OR Manipulate OR manual therapy Or
“Spinal Manipulative Therapy” OR SMT) and (back injury OR
neck pain OR cervical pain OR neck ache OR low back pain OR
low back ache OR spinal OR cervical vertebrae OR coccydynia
OR sciatica OR spondylosis OR lumbago OR whiplash OR lumbar
pain OR lumbar OR sacral OR neck pain OR neck pain* OR
low* backache* OR back ache* OR neck pain* OR neck ache*
OR cervical pain* OR cervical vertebra* OR low* back pain
OR back injur* OR neck injury OR neck injur* OR neck ache*
OR neckache* OR neck pain* OR cervical* OR sciatic*) AND
( ( Clinical Trial[ptyp] OR Pragmatic Clinical Trial[ptyp] OR
Comparative Study[ptyp] OR Controlled Clinical Trial[ptyp]
OR Evaluation Studies[ptyp] OR Multicenter Study[ptyp] OR
Observational Study[ptyp] OR Randomized Controlled Trial[ptyp]
OR Research Support, N I H, Extramural[ptyp] OR Research
Support, Non U S Gov’t[ptyp] OR Research Support, U S Gov’t,
Non P H S[ptyp] OR Research Support, U S Gov’t, P H S[ptyp]
OR Research Support, U.S. Government[ptyp] OR systematic[sb]
OR Practice Guideline[ptyp] OR Meta-Analysis[ptyp] OR
Guideline[ptyp] OR Research Support, N I H, Intramural[ptyp]
OR Validation Studies[ptyp] ) AND ( “2000/01/01”[Pdat] :
“2017/09/28”[Pdat] ) AND Humans[Mesh] AND English[lang]
AND adult[MeSH])
Fig. 1. Search strategy.
Note: Fig. 1 addresses search strategy for neck pain as well as low
back pain studies. The findings of low back pain are not reported
here (32). Because the Center of Excellence for Research in CAM
(CERC) project was focused on both chronic neck pain as well as
chronic low back pain, the search was executed to meet both needs
together to streamline the effort.
 Pain Physician: March/April 2019: 22:E55-E70
Table 1. Eligibility criteria.
Eligibility Criteria Reference Standard Definition
Population “chronic” According to the Pain Management Task Force, (21)
neck pain chronic pain can be described as ongoing or recurrent
pain, lasting beyond the usual course of acute illness or
injury or more than 3-6 months, and which adversely
affects the individual’s well-being. In 2014, the NIH
Task Force on Research Standards for Low Back (22)
recommended defining chronicity of pain as: “How long
has back pain been an ongoing problem for you? (2) How
often has low-back pain been an ongoing problem for
you over the past 6 months? A response of greater than
3 months to question 1, and a response of “at least half
the days in the past 6 months” to question 2 would define
chronic low back pain.”
Population Non-specific pain is defined as pain not attributable
“non-specific” to a recognizable, known specific pathology (23) (e.g.,
infection, tumor, osteoporosis, fracture, structural
deformity, rheumatoid arthritis, radicular syndrome, etc.).
Therefore, the etiology of the pain is often unknown and
it is not categorized with a major pathogenic etiology.
Interventions Bronfort et al. defines mobilization as “the application of
mobilization or manual force to the spinal joints within the passive range
manipulation of joint motion that does not involve a thrust (p. 336).”(8)
The RAND report by Coulter et al. defines mobilization as
“controlled, judiciously applied force of low velocity and
variable amplitude directed to spinal joint segment(s)” (p.
xi).(15,19,20)
Spinal manipulation is defined as “the application of
high-velocity, low amplitude manual thrusts to the spinal
joints slightly beyond the passive range of joint motion,”
by Bronfort et al.,(8) where the RAND report by Coulter
et al. defines spinal manipulation as “a controlled,
judiciously applied dynamic thrust adjustment, that
may include combined extension and rotation of the
upper cervical spinal segments, or low-velocity and
low-amplitude force with the use of a short or long lever
directed to spinal joint segments within patient tolerance”
(p. xi).
Control/ This review focused on any intervention being compared
comparator(s) to mobilization or manipulation, including any active
therapy (i.e., exercise, physical therapy), manipulation
(thrust), mobilization (nonthrust), sham, no-treatment,
usual or standard care.
Outcome(s) Although pain reduction was predefined as the primary
outcome of interest, the most commonly reported pain-
related, patient reported outcomes that affect health status
were determined through a scoping review and thus
pooled to determine which could be assessed.
Study Design(s) All study designs were considered for the purposes of
scoping the literature.
E58 www.painphysicianjournal.com
Scope Driven Evidence-Informed Definition
The majority of studies defined chronicity based on
the duration of pain symptoms for 12 weeks or more.
Therefore, a similar definition of chronicity (≥ 12 weeks)
was adopted, and studies were categorized as those
patients with >12 weeks, a mean duration of 6 months,
and those with >12 months pain duration.
The existing literature does not use standard terminology
to report “non-specific” chronic pain. In order to
guide the eligibility of studies, the following terms were
specified to be outside the scope of “non-specific:” specific
conditions, i.e., cancer, rheumatoid arthritis, fibromyalgia,
spondylolisthesis (displacement of vertebra) and spinal
stenosis (narrowing of spinal canal), temporomandibular
disorders, ankylosing spondylitis, headaches as sole or
principal condition including cervicogenic headache,
etc. Consensus among the internal steering committee
specified the following exemptions: osteoarthritis,
whiplash, radiculopathy, neck pain "of mechanical
origin," pain associated with vertigo, cervico-brachial
pain syndrome, spondylosis, trauma-induced pain, disc
herniation, cervicobrachial, cervico-craniofacial pain, and
"occupational" neck pain.
The interventions in this systematic review consist of
manipulation and/or mobilization in chiropractic settings
and other non-invasive therapies including osteopathy,
manual therapy and physical therapy. For simplicity,
interventions were categorized into thrust and non-
thrust interventions. When combined with other active
interventions, they were labeled as “programs”.
For purpose of analysis, controls/comparisons were
categorized as active, sham, or no treatment, or as direct
comparisons between various thrust or non-thrust
interventions.
Patient-reported outcomes that the majority of studies
include to date: pain intensity/severity (as measured by
a VAS or NRS scale) disability (as measured by the Neck
Disability Index (NDI), health-related quality of life
(HRQoL) as measured by the SF-36/SF-12 and/or safety.
Randomized controlled trials were included in the
systematic review and meta-analysis.
 Manipulation and Mobilization for Treating Chronic Nonspecific Neck Pain
proach, labeled as a “program” if the observed effect
could not be attributed directly to the unimodal thrust
or nonthrust intervention (e.g., a study of chiropractic
plus acupuncture vs. usual care would be multimodal
and labeled as a “program” because chiropractic would
serve as an adjunctive therapy to acupuncture, separate
from chiropractic plus exercise vs. exercise in which the
observed effect could be attributed to the addition of
chiropractic); 3) compared to sham, no treatment or any
other active therapies, such as exercise, physiotherapy,
or physical therapy; and 4) at least one outcome mea-
suring a reduction in pain intensity/severity. Although
all study designs were captured for the scoping of the
literature, only RCTs involving adult human subjects
(aged ≥ 18 years) were considered for this systematic
review and meta-analysis (Table 1).
For simplicity and because eligible studies included
many types and styles of therapies, the authors chose
to refer to the manipulation therapies as “thrust” and
mobilization therapies as “nonthrust.” The studies de-
scribing programs and in which the effects could not
be attributed to thrust or nonthrust alone (multimodal
studies) were separated from those studies in which
the effect could be attributed to thrust or nonthrust
(unimodal studies) for the remainder of the systematic
review methods and to describe the quality of the evi-
dence for included studies.
Quality Assessment and Data Extraction
Risk of bias was assessed independently by 6 re-
viewers in duplicate using the Scottish Intercollegiate
Guidelines Network (SIGN 50) checklist for RCTs (24).
We assessed external and model validity using the
External Validity Assessment Tool (EVAT) (25), which
measures the generalizability of research to other
individuals (external validity) and settings (model
validity) outside a study’s confines. We extracted data
to describe each included study, including the popula-
tion, intervention, control/comparators, and outcomes
at specific timepoints and across various prescribed
doses of treatment.
Data Synthesis and Analysis
Studies were grouped and labeled according to: 1)
duration of chronic pain (i.e., at least 3 months, 6 months,
and 12 months); and 2) studies considered unimodal
with intervention arms consisting of thrust or nonthrust
compared to a sham, no treatment, another active in-
tervention, or a head-to head comparison, or separately,
when combined as a multimodal approach. This group-
www.painphysicianjournal.com E59
ing exercise allowed for the comparison of interventions.
It was also an attempt to reduce heterogeneity.
We extracted data from studies when available for
sample size, and mean and standard deviation for each
treatment group in pain intensity, disability, and HRQoL
outcomes at each timepoint: closest to one month, 3
months, and 6 months. We computed an unbiased
estimate using the Hedges’ effect size (26) and 95%
lower and upper limits, regardless of whether a study
was eligible for meta-analysis for all studies categorized
as unimodal (Appendix Table 1). A negative effect size
indicated a reduction in pain intensity or disability, and
favored manipulation or mobilization. For HRQoL, a
positive effect size indicated an increase in HRQoL with
treatment at those timepoints and favored manipula-
tion or mobilization.
A minimum of 3 studies with sufficient homogene-
ity was considered for meta-analysis. Single treatment
studies (one dose over one day), as well as multimodal
interventions in which the effects of manipulation/
mobilization could not be distinguished from the total
program, were excluded from any attempted pooling
for meta-analysis. For subsets in which authors felt stud-
ies were similar enough to pool and data were available,
standardized mean differences (SMD) were computed
using Comprehensive Meta-Analysis software, Version
3.3.070 (CMA; Biostat, Englewood, NJ). Meta-analyses
of SMD were performed with the generic inverse model
of REVMAN (The Nordic Cochrane Centre for The Co-
chrane Collaboration, Copenhagen, Denmark). We used
random effects models; statistical heterogeneity was
examined by I2 with low, moderate, and high I2 values
of 25%, 50%, and 75%, respectively. We assessed pub-
lication bias using the Begg adjusted rank correlation
test (27) and the Egger regression asymmetry test (28).
Pooled effect sizes for pain and disability outcomes were
translated into the visual analog scale (VAS, 0-100) using
a standard deviation of 25 points, and the neck disabil-
ity index (NDI, 0-50) using a standard deviation of 12.5
points, respectively for clinical interpretation (29,30). For
constructing forest plots, a negative effect size indicated
a reduction in pain intensity or disability and favored
manipulation or mobilization; therefore, the thrust is
on the left side (-) column and active on the right. For
HRQoL, a positive effect size indicated an increase in
HRQoL with treatment at those timepoints and favored
manipulation or mobilization. Therefore, the effect is on
the right side for this outcome (+).
Regardless of whether studies were included in the
meta-analysis or not, we followed the Grading of Recom-
 Pain Physician: March/April 2019: 22:E55-E70

mendations, Assessment, Development, and Evaluation
approach, to determine our confidence in the effects
reported and overall quality of the literature (31).
Results
Our search of multiple databases for studies of
both low back and neck pain yielded 7,460 records (Fig.
2). The systematic review for chronic low back pain has
already been published (32). We report here only on the
47 unique randomized trials (53 publications total) eli-
gible for evaluation related to chronic nonspecific neck
pain. Of these, 37 unique trials (42 publications) (33-74)
were identified as unimodal in which the effect of ma-
nipulation and/or mobilization could be distinguished

Fig. 2. Flow of included studies.

E60 www.painphysicianjournal.com
 Manipulation and Mobilization for Treating Chronic Nonspecific Neck Pain
from that of the comparator. Ten trials (11 publications)
(75-85) were multimodal studies that were designed
more as “programs.” All the studies were included in
the qualitative analysis.
Study Characteristics
Characteristics of included studies are detailed in
Appendix Tables 1 and 2. The 47 included trials examin-
ing either a uni- or multimodal intervention of thrust
and/or nonthrust for patients with chronic nonspecific
neck pain were published between January 2000 and
September 2015. No studies meeting the eligibility cri-
teria were found between January 2016 and September
2017. The total number of patients across the 47 tri-
als was 4,460, ranging from 16 in the smallest to 409
in the largest study. The average age of the patients
was approximately 40 years, ranging from ages 19-65
years. The studies included more men than women. For
unimodal and multimodal studies separately, average
duration of chronic pain ranged from 3 months or more
in 63% and 40% studies, > 6 months in 5% and 20%,
and greater than one year in 32% and 40% of included
trials, respectively.
Of the 37 unimodal studies, 46% were identified
as thrust interventions, 31% as nonthrust interventions,
19% included both thrust and nonthrust intervention
arms, and 4% used a combination of both thrust and
nonthrust as the intervention. The multimodal studies
included combination therapies, such as chiropractic
care, manual and physical therapy combined with
commonly prescribed exercises, massage, ultrasound,
education, or advice in which the effect of the thrust
or nonthrust could not be distinguished from that of
the program. The treatment period of studies was not
consistent and ranged from one day to across 4 months
with as few as a single treatment to up to 20 treatments
over 12 weeks (Appendix Tables 1 and 2).
Studies reported outcomes related to pain inten-
sity/severity, disability, and HRQoL. The most common
outcome measures used were the pain intensity VAS,
the NDI, and the Short Form-36 (SF-36) (Appendix
Tables 1 and 2).
Methodological Quality
According to the SIGN 50 criteria used to assess the
risk of bias, 18 of the 37 unimodal studies were judged
to be of high quality (++), 16 of acceptable quality
(+), and 3 of low quality (0) (Appendix Table 1). The
number of studies that were judged either well covered
or adequately addressed for SIGN 50 criteria included
www.painphysicianjournal.com E61
baseline similarities between groups (36/37) at the start
of the trial, relevant outcomes measured using valid
and reliable methods (35/37), dropout rates (35/37),
intention-to-treat analysis (30/37), an appropriate and
clearly focused question (37/37), randomization pro-
cess (34/37), allocation concealment (27/37), blinding
(31/37), and group differences (33/37). When treatment
was conducted at multiple sites, 4 out of the 5 multisite
studies did not mention if results were comparable
across sites (Table 2). The 10 unique studies evaluating
multimodal approaches for chronic neck pain were all
rated for risk of bias as acceptable quality (+) according
to SIGN 50 RCT criteria (75-80,82-85) (Appendix Table 2).
Categories that were poorly addressed include multisite
similarities (6/10) and group differences (6/10) (Table 2).
In general, we judged that all EVAT categories were
adequately addressed in terms of the recruitment and
participation of those intended for study. However, the
staff, places, and facilities in which the treatment was
being delivered were not always clearly described to
the reader (16/37 unimodal studies and 3/10 multimod-
al studies). Several types of practitioners delivered the
treatment including physical therapists, chiropractors,
and massage therapy students, and in some studies,
multiple therapists delivered the interventions. Treat-
ments were commonly conducted at multiple locations,
as one would often see in real-life practice, including
private clinics, hospitals, and universities (Table 2).
Adverse Events
Of the 37 unimodal RCTs, 12 reported that no
adverse events occurred during the study; 10 reported
minor adverse events, typically transient increases in
pain in the area of treatment or overall soreness. The
remaining 15 studies did not provide any information
on adverse events. Of the 10 multimodal studies, 2
reported minor adverse events such as muscle soreness
or increased pain or tiredness; one study reported that
no adverse events had occurred during the study. The
remaining 7 did not describe any adverse events or
mention whether they occurred during the study (Ap-
pendix Tables 1 and 2).
Multimodal Studies
We did not attempt meta-analysis for the multi-
modal studies given the heterogeneity and varying
combinations of interventions being used for each pro-
gram. Overall, regardless of intervention types, half (n =
5/10) of the studies (76,78,79,81-83) reported a positive
effect on pain outcomes; studies with nonthrust inter-
 Pain Physician: March/April 2019: 22:E55-E70

Table 2. Quality assessment of included studies.

Percentage (n) Unimodal Studies Multimodal Studies
SIGN Criteria Poor Adequate Well NA Poor Adequate Well NA
Appropriate and clearly
- 54% (20) 46% (17) - 10% (1) 60% (6) 30%(3) -
focused question
Randomization 8% (3) 70% (26) 22% (8) - 10% (1) 80% (8) 10% (1) -
Allocation concealment 27% (10) 57% (21) 16% (6) - 20% (2) 80% (8) - -
Blinding 16% (6) 81% (30) 3% (1) 10% (1) 90% (9) - -
Percentage of dropouts 5% (2) 22% (8) 73% (27) - - 40% (4) 60% (6) -
Baseline similarities 3% (1) 35% (13) 62% (23) - 10% (1) 60% (6) 30% (3) -
Group differences 11% (4) 86% (32) 3% (1) - 60% (6) 40% (4) - -
Outcome reliability/validity 5% (2) 22% (8) 73% (27) - - 70% (7) 30% (3) -
Intention-to-treat analyses 19% (7) 16% (6) 65% (24) - 10% (1) 20% (2) 70% (7) -
Multi-site similarities 11% (4) - 3% (1) 86% (32) 60% (6) - - 40% (4)
EVAT Criteria Poor Adequate Well NA Poor Adequate Well NA
Recruitment 8% (3) 92% (34) - - - 100% (10) - -
Participation 14% (5) 49% (18) 37% (14) - 10% (1) 80% (8) 10% (1) -
Model Validity 43% (16) 35% (13) - 22% (8) 30% (3) 50% (5) 10% (1) 10% (1)

Fig. 3. Reduction in pain.

E62 www.painphysicianjournal.com
 Manipulation and Mobilization for Treating Chronic Nonspecific Neck Pain
Fig. 4. Reduction in disability.
ventions trended toward greater pain reductions than
did interventions with thrust. Of the 8 studies mea-
suring disability as an outcome, 7 reported improved
function using a multimodal approach; only one study
assessed HRQoL as an outcome (Appendix Table 2).
Unimodal Studies
The unimodal studies published since January 2000
comparing thrust to either sham (n = 5) or no treat-
ment (n = 3) included treatment of one dose/one day
(n = 5/8 studies) or varied in duration or types of inter-
ventions/comparators, which prevented pooling. These
studies have small samples and show mixed results for
a reduction in pain; only one study measured disability
and 2 studied HRQoL. The studies comparing nonthrust
to either sham or no treatment (n = 4) were all of one
dose/one day treatment; 3 of the 4 studies did not
www.painphysicianjournal.com E63
show any immediate reduction in pain; only one study
assessed disability as an outcome. The studies compar-
ing nonthrust to active comparators were also either
one dose/one day treatment or compared interventions
too different to pool (n = 4). There were also studies
comparing different styles or doses of thrust and/or
nonthrust (Appendix Table 1).
There were 6 studies the authors believed could
be combined and compared thrust interventions that
included an exercise regimen to exercise alone at
timepoints closest to 1, 3, and 6 months follow-up. The
authors believed meta-analysis could be attempted for
the outcomes of pain, disability, and HRQoL (Figs. 3-5).
The pooled SMD across 5 studies (535 patients) closest
to one month showed a nonstatistically significant re-
duction in pain in favor of thrust plus exercise versus
exercise regimen alone (SMD = –0.37; 95% confidence
 Pain Physician: March/April 2019: 22:E55-E70
Fig. 5. Enhanced health-related quality of life.
interval [CI], –0.77 to 0.03; P = 0.07; I2 = 81%). Translated
into the VAS, this equates to a 9.25-point change on a
0-100 scale. A similar effect is noted (SMD = –0.27; 95%
CI, –0.60 to 0.06; P = 0.10; I2 = 64%) at 3 months across 5
studies (481 patients); at 6 months even less of an effect
is observed across 4 trials (473 patients) (SMD = –0.20;
95% CI, –0.54 to 0.14; P = 0.25; I2 = 70%) (Fig. 3). Across
these same studies, meta-analysis produced similar re-
sults for a reduction in disability. At the timepoint near-
est one month, a nonstatistically significant reduction
in disability favored thrust plus exercise compared to
exercise alone (SMD = –0.35; 95% CI, –0.76 to 0.06; P =
0.09; I2 = 81%). Translated into the NDI, this equates to
a 4.4-point change on a 0-50 scale. SMD for a reduction
in disability at 3 months (SMD = –0.35; 95% CI, –0.70 to
0.00; P = 0.05; I2 = 68%), and at 6 months across 3 trials
(473 patients) (SMD = –0.12; 95% CI, –0.33 to 0.08; P =
0.23; I2 = 18%) (Fig. 4). HRQoL was pooled across 3 stud-
ies closest to 1, 3, and 6 months (405 patients); at one
month (SMD = 0.19; 95% CI, –0.28 to 0.66; P = 0.43; I2 =
E64 www.painphysicianjournal.com
82%); at 3 months (SMD = 0.25; 95% CI, –0.30 to 0.80; P
= 0.38; I2 = 87%), and at 6 months (SMD = 0.07; 95% CI,
–0.46 to 0.59; P = 0.80; I2 = 86%) (Fig. 5).
Confidence in the Effect Estimates
Overall, risk of bias was not of serious concern
across all studies evaluated for systematic review. Meth-
odological quality of studies since 2000 is adequate.
However, heterogeneity was of serious concern for
this systematic review, and results are not consistent
across included studies. Clinical heterogeneity hindered
our ability to pool attempted subsets or categories of
studies and comparators as well as varying interven-
tion approaches, treatment doses, and duration of
studies reported in the literature. There were only 6
studies for which the authors judged meta-analysis to
be feasible. The studies looked at the effect of thrust
plus exercise versus exercise alone at timepoints of 1, 3,
and 6 months. As expected, we detected a statistically
significant degree of heterogeneity in these pooled
 Manipulation and Mobilization for Treating Chronic Nonspecific Neck Pain
studies’ analyses except for closest to 6 months for
disability when the studies similarly report small or no
effect favoring either approach. Outcomes measures,
however, appear consistent, and report the VAS, NDI,
and SF-36 tools at varying timepoints. Sample sizes re-
mained small across studies. Although the studies were
directly related to our research question, inconsistency
and small sample size contributed to overall impreci-
sion. We did not detect any publication bias according
to either the Begg or Egger tests according to group-
ings (data not shown). Considering these factors, our
confidence in the effect estimates are limited, and we
graded the overall literature pool as low to moderate
quality evidence. Our evaluation and Appendix Tables
1 and 2 display these different approaches preventing
pooling.
Discussion
There is low to moderate quality evidence that
various types of manipulation and/or mobilization will
reduce pain and improve function for chronic nonspe-
cific neck pain compared to other interventions. Many
of the previous reviews of chronic nonspecific neck pain
report evidence in favor of manipulation and mobiliza-
tion for patients with chronic neck pain. However, most
of these studies also report that methodological flaws
render the evidence insufficient or inconclusive, mak-
ing it inappropriate to conclude that manipulation and/
or mobilization are more effective compared to usual
care or other CIM therapies.
We relied on the evidence from previous reviews
(8,15,19,20) as a starting point for this review. The
Shekelle and Coulter (15) review found that there is
greater evidence for manipulation and mobilization
of chronic low back pain compared to chronic neck
pain. Both the Bronfort et al (8) systematic review
and the Shekelle and Coulter (15) systematic review
emphasized the need for future trials to examine well-
defined subgroups of patients, and to further assess
the value of manipulation and mobilization to estab-
lish the optimal number of treatment visits. In 2010,
Gross et al (5) published a Cochrane Review on ma-
nipulation and mobilization of neck pain. The Gross
et al (5) review reported conclusions similar to those
in our review and in the Bronfort et al (8) systematic
review (i.e., moderate evidence that thrust/nonthrust
is equal to or superior to general practitioner manage-
ment for short-term pain reduction for chronic neck
pain patients).
Other systematic reviews (12,86) have also found
www.painphysicianjournal.com E65
that therapies involving manual therapy (thrust/non-
thrust) and exercise are more effective than other non-
invasive alternative strategies for patients with chronic
neck pain. Vernon et al (87,88) published 2 systematic
reviews on neck pain. They indicated moderate to
high quality evidence in support of spinal manipula-
tion or mobilization for chronic nonspecific neck pain
(8,15,19,20,87).
Strengths and Limitations
Although this review builds on previous efforts,
it adds to the literature base by including both ma-
nipulation and mobilization interventions not only in
chiropractic settings, but in other noninvasive therapy
settings such as osteopathy, manual therapy, and physi-
cal therapy. We attempted to sort the literature in the
most homogeneous fashion, predefining eligibility
criteria and specifying precise definitions with subject
matter experts. Still, few studies could be pooled for
meta-analysis. The methodological quality of studies
published since 2000 appears to be adequate overall;
few studies suffered from methodological flaws that
would risk biasing the reported results. However, the
studies remain heterogeneous in terms of dose, styles of
interventions, controls/comparators being used across
studies, and chronicity of patients is not always consis-
tently defined across studies included. We attempted
to create homogeneous subsets of data through the
current analysis. Doing so may have reduced the power
of calculations when only a small number of studies
could be pooled. Further research is likely to have an
important impact on the evidence.
Most systematic reviews that evaluate treatment
efficacy for musculoskeletal disorders such as chronic
neck pain give preference to including unimodal rather
than multimodal approaches. As noted previously,
studies with unimodal approaches can better isolate
(statistically) the individual effects of mobilization
and manipulation. In contrast, assessing the effect of
multimodal programs can be problematic, especially
when meta-analysis is desired. However, multimodal
programs may better represent “real-world” clinical
practice and may translate to clearer clinical knowledge
(89).
The approaches used in the multimodal interven-
tion studies are heterogeneous between, and in some
cases within, individual studies. Some studies evaluate a
specific standard program; some evaluate classification-
based approaches in which patients are assigned thera-
pies based on an assessment of the etiology of their
 Pain Physician: March/April 2019: 22:E55-E70
pain; and some are pragmatic trials that allow practi-
tioners to choose specific treatments for each patient.
Because the study of multimodal programs is more dif-
ficult than that for unimodal interventions, largely ow-
ing to their heterogeneity, it is difficult to interpret the
evidence. However, these types of approaches are more
likely what one would see in practice (90). As groups
such as chiropractors are accepted more widely in such
treatment settings and hospitals, the norm is likely to be
multimodal care. The majority of nonthrust multimodal
studies trended toward showing significant pain reduc-
tion results compared to that of the thrust multimodal
studies. However, additional treatment modalities (e.g.,
prescribed exercises, stretches, massage, ultrasound,
education, or advice) were used in conjunction with
manual manipulation and mobilization treatments, so
the causal link between treatment and clinical effect
cannot be substantiated. This trend is also in contrast to
the unimodal studies, in which thrust interventions may
appear to be more effective than nonthrust in reducing
pain intensity.
The research to support manipulation and mobili-
zation as a treatment for chronic nonspecific neck pain
is complicated and trying to dissect it to draw specific
conclusions proved challenging. Stakeholders, includ-
ing physicians and their patients, should have an active
voice at the table when identifying what will be most
impactful to them and building future research agen-
das. This review can serve as a guide to the categories
of studies with strength areas for treating chronic neck
pain with manipulation and mobilization, and the set-
tings in which multimodal approaches were incorpo-
rated in which there may be an increased benefit to
the patient.
Although the focus of this review was on random-
ized trials, it is important to note that available research
on manipulation and mobilization for the treatment of
chronic nonspecific neck pain encompasses study de-
signs other than the randomized controlled trial (e.g.,
cohort studies [both perspective and retrospective], ob-
servational studies, and others). The use of observation-
Appendix
Appendix Table 1
Appendix Table 2
To view pdf with Appendix links active, visit
Pain Physician journal website
to access manuscript pdf.
E66 www.painphysicianjournal.com
al studies is important for building the evidence base in
which randomized trials are lacking or are insufficient
for the task (e.g., assessing adverse effects, identifying
best practices, and understanding disparities in access
to and delivery of health care services).
Conclusions
There is low to moderate quality evidence that
various types of manipulation and/or mobilization will
reduce pain and improve function for chronic nonspe-
cific neck pain compared to other interventions. The
methodological quality of the reported trials from 2000
to 2017 is adequate to evaluate. The studies remain het-
erogeneous in terms of dosing, duration of treatment,
interventions, and comparators. For these reasons, it
remains a challenge to draw conclusions and have con-
fidence in any estimated effect that could be confirmed
as a benefit of mobilization and manipulation alone for
chronic neck pain beyond other therapies. Based only
on the trial literature to date, these therapies do ap-
pear to be safe. However, large longitudinal studies are
needed to establish safety.
Acknowledgments
The authors would like to acknowledge the follow-
ing individuals for their technical and administrative
support throughout the project: Cindy Lentino, Viviane
Enslein, Chris Baur, John Bingham, Holly Chittum, Lau-
rie Davidson, and Judy Bearer.
Author contributions: Dr. Ian Coulter had full access
to all the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data
analyses. Drs. Coulter, Vernon, Hurwitz, and Herman—
with the support of Ms. Crawford and Dr. Khorsan—
designed the study protocol. Ms. Crawford, Ms. Booth,
and Dr. Khorsan managed the literature searches and
summaries of previous related work and wrote the first
draft of the manuscript. Drs. Coulter, Vernon, Hurwitz,
and Herman provided revision for intellectual content
and final approval of the manuscript.
 Manipulation and Mobilization for Treating Chronic Nonspecific Neck Pain
References
1. Cote P, Cassidy JD, Carroll L; The Sas-
katchewan Health and Back Pain Survey.
The prevalence of neck pain and related
disability in Saskatchewan adults. Spine
(Phila Pa 1976) 1998; 23:1689-1698.
2. Martin BI, Gerkovich MM, Deyo RA,
Sherman KJ, Cherkin DC, Lind BK, Go-
ertz CM, Lafferty WE. The association of
complementary and alternative medi-
cine use and health care expenditures
for back and neck problems. Med Care
2012; 50:1029-1036.
3. Borghouts JA, Koes BW, Vondeling H,
Bouter LM. Cost-of-illness of neck pain
in The Netherlands in 1996. Pain 1999;
80:629-636.
4. Korthals-de Bos IB, Hoving JL, van Tul-
der MW, Rutten-van Molken MP, Ader
HJ, de Vet HC, Koes BW, Vondeling H,
Bouter LM. Cost effectiveness of phys-
iotherapy, manual therapy, and general
practitioner care for neck pain: Econom-
ic evaluation alongside a randomised
controlled trial. BMJ 2003; 326:911.
5. Gross A, Miller J, D’Sylva J, Burnie SJ,
Goldsmith CH, Graham N, Haines T,
Bronfort G, Hoving JL. Manipulation or
mobilisation for neck pain: A Cochrane
Review. Man Ther 2010; 15:315-333.
6. Evans G. Identifying and treating the
causes of neck pain. Med Clin North Am
2014; 98:645-661.
7. Cohen S, Hooten W. Advances in the di-
agnosis and management of neck pain.
BMJ 2017; 358.
8. Bronfort G, Haas M, Evans RL, Bouter
LM. Efficacy of spinal manipulation and
mobilization for low back pain and neck
pain: A systematic review and best evi-
dence synthesis. Spine J 2004; 4:335-356.
9. Peloso P, Gross A, Haines T, Trinh K,
Goldsmith CH, Burnie S; Cervical Over-
view Group. Medicinal and injection
therapies for mechanical neck disor-
ders. Cochrane Database Syst Rev 2007;
3:CD000319.
10. Carragee EJ, Hurwitz EL, Cheng I, Car-
roll LJ, Nordin M, Guzman J, Peloso P,
Holm LW, Cote P, Hogg-Johnson S, van
der Velde G, Cassidy JD, Haldeman S;
Bone and Joint Decade 2000-2010 Task
Force on Neck Pain and Its Associated
Disorders. Treatment of neck pain: In-
jections and surgical interventions:
Results of the Bone and Joint Decade
2000-2010 Task Force on Neck Pain and
Its Associated Disorders. Spine 2008;
www.painphysicianjournal.com E67
33(4 Suppl):S153-169.
11. Brison RJ, Hartling L, Dostaler S, Leger
A, Rowe BH, Stiell I, Pickett W. A ran-
domized controlled trial of an educa-
tional intervention to prevent the chron-
ic pain of whiplash associated disorders
following rear-end motor vehicle colli-
sions. Spine 2005; 30:1799-1807.
12. Hurwitz EL, Carragee EJ, van der Velde
G, Carroll LJ, Nordin M, Guzman J, Pe-
loso PM, Holm LW, Cote P, Hogg-John-
son S, Cassidy JD, Haldeman S; Bone
and Joint Decade 2000-2010 Task Force
on Neck Pain and Its Associated Disor-
ders. Treatment of neck pain: Noninva-
sive interventions: Results of the Bone
and Joint Decade 2000-2010 Task Force
on Neck Pain and Its Associated Disor-
ders. Spine 2008; 33(4 Suppl):S123-152.
13. Schroeder J, Kaplan L, Fischer DJ, Skelly
AC. The outcomes of manipulation or
mobilization therapy compared with
physical therapy or exercise for neck
pain: A systematic review. Evid Based
Spine Care J 2013; 4:30-41.
14. Gross A, Langevin P, Burnie SJ, Bédard-
Brochu MS, Empey B, Dugas E, Faber-
Dobrescu M, Andres C, Graham N,
Goldsmith CH, Brønfort G, Hoving JL,
LeBlanc F. Manipulation and mobiliza-
tion for neck pain contrasted against an
inactive control or another active treat-
ment. Cochrane Database Syst Rev 2015;
9:CD004249.
15. Shekelle PG, Coulter I. Cervical spine
manipulation: Summary report of a sys-
tematic review of the literature and a
multidisciplinary expert panel. J Spinal
Disord 1997; 10:223-228.
16. Bryans R, Decina P, Descarreaux M,
Duranleau M, Marcoux H, Potter B,
Ruegg RP, Shaw L, Watkin R, White E.
Evidence-based guidelines for the chi-
ropractic treatment of adults with neck
pain. J Manipulative Physiol Ther 2014;
37:42-63.
17. Vincent K, Maigne JY, Fischhoff C, Lan-
lo O, Dagenais S. Systematic review of
manual therapies for nonspecific neck
pain. Joint Bone Spine 2013; 80:508-515.
18. Furlan AD, Yazdi F, Tsertsvadze A, Gross
A, Van Tulder M, Santaguida L, Gagnier
J, Ammendolia C, Dryden T, Doucette
S, Skidmore B, Daniel R, Ostermann
T, Tsouros S. A systematic review and
meta-analysis of efficacy, cost-effective-
ness, and safety of selected complemen-
tary and alternative medicine for neck
and low-back pain. Evid Based Comple-
ment Alternat Med 2012; 2012:953139.
19. Shekelle PG, Adams AH, Chassin MR,
Hurwitz EL, Brook RH. Spinal manipu-
lation for low-back pain. Ann Intern Med
1992; 117:590-598.
20. Shekelle PG, Hurwitz EL, Coulter I, Ad-
ams AH, Genovese B, Brook RH. The
appropriateness of chiropractic spinal
manipulation for low back pain: A pilot
study. J Manipulative Physiol Ther 1995;
18:265-270.
21. Office of the Army Surgeon General:
Pain Management Task Force. Pain
Management Task Force Final Report:
Providing a Standardized DoD and VHA
Vision and Approach to Pain Management
to Optimize the Care for Warriors and their
Families. Washington, DC: Office of the
Army Surgeon General; 2010.
22. Deyo RA, Dworkin SF, Amtmann D, An-
dersson G, Borenstein D, Carragee E,
Carrino J, Chou R, Cook K, DeLitto A,
Goertz C, Khalsa P, Loeser J, Mackey S,
Panagis J, Rainville J, Tosteson T, Turk D,
Von Korff M, Weiner DK. Report of the
NIH Task Force on research standards
for chronic low back pain. J Pain 2014;
15:569-585.
23. Maher C, Underwood M, Buchbinder R.
Non-specific low back pain. Lancet 2017;
389:736-747.
24. Scottish Intercollegiate Guidelines Net-
work. Sign 50: A Guideline Developer’s
Handbook. 2010 [cited 2015 Jan 1]; Avail-
able from: www.sign.ac.uk/. Accessed
March 10, 2019.
25. Khorsan R, Crawford C. How to assess
the external validity and model validity
of therapeutic trials: A conceptual ap-
proach to systematic review methodol-
ogy. Evid Based Complement Alternat Med
2014; 2014:694804.
26. Hedges LV, Olkin I. Statistical Methods
for Meta-Analysis. Orlando, FL: Academ-
ic Press; 1985.
27. Begg CB, Mazumdar M. Operating
characteristics of a rank correlation test
for publication bias. Biometrics 1994;
50:1088-1101.
28. Egger M, Davey Smith G, Schneider M,
Minder C. Bias in meta-analysis detect-
ed by a simple, graphical test. BMJ 1997;
315:629-634.
29. Assendelft WJ, Morton SC, Yu EI, Sut-
torp MJ, Shekelle PG. Spinal manipu-
lative therapy for low back pain. A me-
 Pain Physician: March/April 2019: 22:E55-E70
ta-analysis of effectiveness relative to
other therapies. Ann Intern Med 2003;
138:871-881.
30. Vernon H. The Neck Disability Index:
State of the art, 1991-2008. J Manipula-
tive Physiol Ther 2008; 31:491-502.
31. GRADE Working Group. Grading of Rec-
ommendations Assessment, Development
and Evaluation (GRADE). November
30, 2011; Available from: www.grade-
workinggroup.org/. Accessed March 10,
2019.
32. Coulter ID, Crawford C, Hurwitz EL,
Vernon H, Khorsan R, Suttorp Booth
M, Herman PM. Manipulation and mo-
bilization for treating chronic low back
pain: A systematic review and meta-
analysis. Spine J 2018; 18:866-879.
33. Akhter S, Khan M, Ali SS, Soomro RR.
Role of manual therapy with exercise
regime versus exercise regime alone in
the management of non-specific chron-
ic neck pain. Pak J Pharm Sci 2014; 27(6
Suppl):2125-2128.
34. Aquino RL, Caires PM, Furtado FC,
Loureiro AV, Ferreira PH, Ferreira ML.
Applying joint mobilization at differ-
ent cervical vertebral levels does not
influence immediate pain reduction in
patients with chronic neck pain: A ran-
domized clinical trial. J Man Manip Ther
2009; 17:95-100.
35. Briem K, Huijbregts P, Thorsteinsdottir
M. Immediate effects of inhibitive dis-
traction on active range of cervical flex-
ion in patients with neck pain: A pilot
study. J Man Manip Ther 2007; 15:82-92.
36. Bronfort G, Evans R, Nelson B, Aker PD,
Goldsmith CH, Vernon H. A random-
ized clinical trial of exercise and spinal
manipulation for patients with chronic
neck pain. Spine (Phila Pa 1976) 2001;
26:788-797; discussion 798-799.
37. Cleland JA, Childs JD, McRae M, Palmer
JA, Stowell T. Immediate effects of tho-
racic manipulation in patients with neck
pain: A randomized clinical trial. Man
Ther 2005; 10:127-135.
38. Dunning JR, Cleland JA, Waldrop MA,
Arnot C, Young I, Turner M, Sigurdsson
G. Upper cervical and upper thoracic
thrust manipulation versus nonthrust
mobilization in patients with mechani-
cal neck pain: A multicenter randomized
clinical trial. J Orthop Sports Phys Ther
2012; 42:5-18.
39. Dziedzic K, Hill J, Lewis M, Sim J, Dan-
iels J, Hay EM. Effectiveness of manual
therapy or pulsed shortwave diathermy
in addition to advice and exercise for
E68 www.painphysicianjournal.com
neck disorders: A pragmatic random-
ized controlled trial in physical therapy
clinics. Arthritis Rheum 2005; 53:214-222.
40. Escortell-Mayor E, Riesgo-Fuertes R,
Garrido-Elustondo S, Asunsolo-Del
Barco A, Diaz-Pulido B, Blanco-Diaz M,
Bejerano-Alvarez E. Primary care ran-
domized clinical trial: Manual therapy
effectiveness in comparison with TENS
in patients with neck pain. Man Ther
2011; 16:66-73.
41. Evans R, Bronfort G, Nelson B, Gold-
smith CH. Two-year follow-up of a
randomized clinical trial of spinal ma-
nipulation and two types of exercise for
patients with chronic neck pain. Spine
(Phila Pa 1976) 2002; 27:2383-2389.
42. Evans R, Bronfort G, Schulz C, Maiers
M, Bracha Y, Svendsen K, Grimm R,
Garvey T, Transfeldt E. Supervised exer-
cise with and without spinal manipula-
tion performs similarly and better than
home exercise for chronic neck pain: A
randomized controlled trial. Spine 2012;
37:903-914.
43. Hemmila HM. Bone setting for pro-
longed neck pain: A randomized clini-
cal trial. J Manipulative Physiol Ther 2005;
28:508-515.
44. Hurwitz EL, Goldstein MS, Morgenstern
H, Chiang LM. The impact of psychoso-
cial factors on neck pain and disability
outcomes among primary care patients:
Results from the UCLA Neck Pain Study.
Disabil Rehabil 2006; 28:1319-1329.
45. Hurwitz EL, Morgenstern H, Harber P,
Kominski GF, Yu F, Adams AH. A ran-
domized trial of chiropractic manipu-
lation and mobilization for patients
with neck pain: Clinical outcomes from
the UCLA neck-pain study. Am J Public
Health 2002; 92:1634-1641.
46. Hurwitz EL, Morgenstern H, Vassilaki
M, Chiang L. Adverse reactions to chi-
ropractic treatment and their effects
on satisfaction and clinical outcomes
among patients enrolled in the UCLA
Neck Pain Study. J Manipulative Physiol
Ther 2004; 27:16-25.
47. Hurwitz EL, Morgenstern H, Vassilaki
M, Chiang L. Frequency and clinical
predictors of adverse reactions to chi-
ropractic care in the UCLA Neck Pain
Study. Spine 2005; 30:1477-1484.
48. Izquierdo Perez H, Alonso Perez JL, Gil
Martinez A, La Touche R, Lerma-Lara S,
Commeaux Gonzalez N, Arribas Perez
H, Bishop MD, Fernandez-Carnero J. Is
one better than another? A randomized
clinical trial of manual therapy for pa-
tients with chronic neck pain. Man Ther
2014; 19:215-221.
49. Kanlayanaphotporn R, Chiradejnant A,
Vachalathiti R. The immediate effects
of mobilization technique on pain and
range of motion in patients presenting
with unilateral neck pain: A randomized
controlled trial. Arch Phys Med Rehabil
2009; 90:187-192.
50. Kanlayanaphotporn R, Chiradejnant A,
Vachalathiti R. Immediate effects of the
central posteroanterior mobilization
technique on pain and range of motion
in patients with mechanical neck pain.
Disabil Rehabil 2010; 32:622-628.
51. Klein R, Bareis A, Schneider A, Linde K.
Strain-counterstrain to treat restrictions
of the mobility of the cervical spine in
patients with neck pain: A sham-con-
trolled randomized trial. Complement
Ther Med 2013; 21:1-7.
52. Lau HM, Wing Chiu TT, Lam TH. The ef-
fectiveness of thoracic manipulation on
patients with chronic mechanical neck
pain: A randomized controlled trial. Man
Ther 2011; 16:141-147.
53. Lin JH, Shen T, Chung RCK, Chiu TTW.
The effectiveness of Long’s manipula-
tion on patients with chronic mechani-
cal neck pain: A randomized controlled
trial. Man Ther 2013; 18:308-315.
54. Lluch E, Schomacher J, Gizzi L, Petzke
F, Seegar D, Falla D. Immediate effects
of active cranio-cervical flexion exercise
versus passive mobilisation of the upper
cervical spine on pain and performance
on the cranio-cervical flexion test. Man
Ther 2014; 19:25-31.
55. Lopez-Lopez A, Alonso Perez JL, Gon-
zalez Gutierez JL, La Touche R, Lerma
Lara S, Izquierdo H, Fernandez-Carnero
J. Mobilization versus manipulations
versus sustain apophyseal natural glide
techniques and interaction with psycho-
logical factors for patients with chronic
neck pain: Randomized controlled trial.
Eur J Phys Rehabil Med 2015; 51:121-132.
56. Madson TJ, Cieslak KR, Gay RE. Joint
mobilization vs massage for chronic
mechanical neck pain: A pilot study to
assess recruitment strategies and esti-
mate outcome measure variability. J Ma-
nipulative Physiol Ther 2010; 33:644-651.
57. Marks M, Schottker-Koniger T, Probst
A. Efficacy of cervical spine mobili-
zation versus peripheral nerve slider
techniques in cervicobrachial pain syn-
drome: A randomized clinical trial. J
Phys Ther 2011; 4:9-17.
58. Martel J, Dugas C, Dubois JD, Descar-
 Manipulation and Mobilization for Treating Chronic Nonspecific Neck Pain
reaux M. A randomised controlled trial
of preventive spinal manipulation with
and without a home exercise program
for patients with chronic neck pain.
BMC Musculoskelet Disord 2011; 12:41.
59. Martinez-Segura R, De-la-Llave-Rincon
AI, Ortega-Santiago R, Cleland JA, Fer-
nandez-de-las-Penas C. Immediate
changes in widespread pressure pain
sensitivity, neck pain, and cervical range
of motion after cervical or thoracic
thrust manipulation in patients with bi-
lateral chronic mechanical neck pain: A
randomized clinical trial. J Orthop Sports
Phys Ther 2012; 42:806-814.
60. Martínez-Segura R, Fernández-de-las-
Peñas C, Ruiz-Sáez M, López-Jiménez C,
Rodríguez-Blanco C. Immediate effects
on neck pain and active range of mo-
tion after a single cervical high-velocity
low-amplitude manipulation in subjects
presenting with mechanical neck pain: A
randomized controlled trial. J Manipula-
tive Physiol Ther 2006; 29:511-517.
61. Murphy B, Taylor HH, Marshall P. The
effect of spinal manipulation on the ef-
ficacy of a rehabilitation protocol for
patients with chronic neck pain: A pilot
study. J Manipulative Physiol Ther 2010;
33:168-177.
62. Pires PF, Packer AC, Dibai-Filho AV,
Rodrigues-Bigaton D. Immediate and
short-term effects of upper thoracic
manipulation on myoelectric activity of
sternocleidomastoid muscles in young
women with chronic neck pain: A ran-
domized blind clinical trial. J Manipula-
tive Physiol Ther 2015; 38:555-563.
63. Saavedra-Hernandez M, Arroyo-Mo-
rales M, Cantarero-Villanueva I, Fer-
nandez-Lao C, Castro-Sanchez AM, Pu-
entedura EJ, Fernandez-de-las-Penas C.
Short-term effects of spinal thrust joint
manipulation in patients with chronic
neck pain: A randomized clinical trial.
Clin Rehabil 2013; 27:504-512.
64. Saavedra-Hernández M, Castro-Sán-
chez AM, Arroyo-Morales M, Cleland JA,
Lara-Palomo I, Fernández-de-las-Peñas
C. Short-term effects of kinesio taping
versus cervical thrust manipulation in
patients with mechanical neck pain: A
randomized clinical trial. J Orthop Sports
Phys Ther 2012; 42:724-730.
65. Saayman L, Hay C, Abrahamse H. Chi-
ropractic manipulative therapy and low-
level laser therapy in the management
of cervical facet dysfunction: A random-
ized controlled study. J Manipulative
Physiol Ther 2011; 34:153-163.
www.painphysicianjournal.com E69
66. Salom-Moreno J, Ortega-Santiago R,
Cleland JA, Palacios-Cena M, Truyols-
Dominguez S, Fernandez-de-las-Penas
C. Immediate changes in neck pain in-
tensity and widespread pressure pain
sensitivity in patients with bilateral
chronic mechanical neck pain: A ran-
domized controlled trial of thoracic
thrust manipulation vs non-thrust mo-
bilization. J Manipulative Physiol Ther
2014; 37:312-319.
67. Schwerla F, Bischoff A, Nurnberger A,
Genter P, Guillaume JP, Resch KL. Os-
teopathic treatment of patients with
chronic non-specific neck pain: A ran-
domised controlled trial of efficacy.
Forsch Komplementmed 2008; 15:138-145.
68. Sillevis R, Cleland J. Immediate effects
of the audible pop from a thoracic spine
thrust manipulation on the autonomic
nervous system and pain: A secondary
analysis of a randomized clinical trial. J
Manipulative Physiol Ther 2011; 34:37-45.
69. Sillevis R, Cleland J, Hellman M,
Beekhuizen K. Immediate effects of a
thoracic spine thrust manipulation on
the autonomic nervous system: A ran-
domized clinical trial. J Man Manip Ther
2010; 18:181-190.
70. Snodgrass SJ, Rivett DA, Sterling M, Vi-
cenzino B. Dose optimization for spinal
treatment effectiveness: A randomized
controlled trial investigating the effects
of high and low mobilization forces in
patients with neck pain. J Orthop Sports
Phys Ther 2014; 44:141-152.
71. Suvarnnato T, Puntumetakul R, Kaber
D, Boucaut R, Boonphakob Y, Arayaw-
ichanon P, Chatchawan U. The effects of
thoracic manipulation versus mobiliza-
tion for chronic neck pain: A random-
ized controlled trial pilot study. J Phys
Ther Sci 2013; 25:865-871.
72. Vernon HT, Triano JJ, Ross JK, Tran SK,
Soave DM, Dinulos M.D. Validation of
a novel sham cervical manipulation pro-
cedure. Spine J 2012; 12:1021-1028.
73. Wood TG, Collaca CJ, Matthews R. A
pilot randomized clinical trial on the
relative effect of instrumental (MFMA)
versus manual (HVLA) manipulation in
the treatment of cervical spine dysfunc-
tion. J Manipulative Physiol Ther 2001;
24:260-271.
74. Zaproudina N, Hanninen OO, Airaksin-
en O. Effectiveness of traditional bone
setting in chronic neck pain: Random-
ized clinical trial. J Manipulative Physiol
Ther 2007; 30:432-437.
75. Allan M, Brantingham JW, Menezes A.
Stretching as an adjunct to chiroprac-
tic manipulation of chronic neck pain-
-before, after or not at all? A prospective
randomized controlled clinical trial. Eur
J Chiropr 2003; 50:41-52.
76. Allison GT, Nagy BM, Hall T. A random-
ized clinical trial of manual therapy for
cervico-brachial pain syndrome: A pilot
study. Man Ther 2002; 7:95-102.
77. Gustavsson C, Denison E, Koch Lv.
Self-management of persistent neck
pain: A randomized controlled trial of
a multi-component group intervention
in primary health care. Eur J Pain 2010;
14:630.e1-630.e11.
78. Klaber Moffett JA, Jackson DA, Rich-
mond S, Hahn S, Coulton S, Farrin A,
Manca A, Torgerson DJ. Randomised tri-
al of a brief physiotherapy intervention
compared with usual physiotherapy for
neck pain patients: Outcomes and pa-
tients’ preference. BMJ 2005; 330:75.
79. Nee RJ, Vicenzino B, Jull GA, Cleland JA,
Coppieters MW. Neural tissue manage-
ment provides immediate clinically rel-
evant benefits without harmful effects
for patients with nerve-related neck and
arm pain: A randomised trial. J Physio-
ther 2012; 58:23-31.
80. Palmgren PJ, Sandstrom PJ, Lundqvist
FJ, Heikkila H. Improvement after chi-
ropractic care in cervicocephalic kin-
esthetic sensibility and subjective pain
intensity in patients with nontraumatic
chronic neck pain. J Manipulative Physiol
Ther 2006; 29:100-106.
81. Skillgate E, Bohman T, Holm LW, Vin-
gard E, Alfredsson L. The long-term
effects of naprapathic manual therapy
on back and neck pain: Results from a
pragmatic randomized controlled trial.
BMC Musculoskelet Disord 2010; 11:26.
82. Skillgate E, Vingard E, Alfredsson L. Na-
prapathic manual therapy or evidence-
based care for back and neck pain: A
randomized, controlled trial. Clin J Pain
2007; 23:431-439.
83. Walker MJ, Boyles RE, Young BA,
Strunce JB, Garber MB, Whitman JM,
Deyle G, Wainner RS. The effectiveness
of manual physical therapy and exercise
for mechanical neck pain: A randomized
clinical trial. Spine (Phila Pa 1976) 2008;
33:2371-2378.
84. Ylinen J, Kautiainen H, Wiren K, Hak-
kinen A. Stretching exercises vs manual
therapy in treatment of chronic neck
pain: A randomized, controlled cross-
over trial. J Rehabil Med 2007; 39:126-132.
 Pain Physician: March/April 2019: 22:E55-E70

85. Young IA, Michener LA, Cleland JA,
Aguilera AJ, Snyder AR. Manual therapy,
exercise, and traction for patients with
cervical radiculopathy: A randomized
clinical trial. Phys Ther 2009; 89:632-642.
86. Miller J, Gross A, D’Sylva J, Burnie SJ,
Goldsmith CH, Graham N, Haines T,
Bronfort G, Hoving JL. Manual therapy
and exercise for neck pain: A systematic
review. Man Ther 2010; 15:334-354.
87. Vernon H, Humphreys K, Hagino C.
Chronic mechanical neck pain in adults
treated by manual therapy: A systematic
review of change scores in randomized
clinical trials. J Manipulative Physiol Ther
2007; 30:215-227.
88. Vernon H, Humphreys BK. Manual
therapy for neck pain: An overview of
randomized clinical trials and system-
atic reviews. Eura Medicophys 2007;
43:91-118.
89. Jull G, Moore A. Systematic reviews as-
sessing multimodal treatments. Man
Ther 2010; 15:303-304.
90. Goertz CM, Long CR, Vining RD, Pohl-
man KA, Kane B, Corber L, Walter J,
Coulter I. Assessment of chiropractic
treatment for active duty, U.S. military
personnel with low back pain: Study
protocol for a randomized controlled
trial. Trials 2016; 17:70.

E70 www.painphysicianjournal.com